Cellular proliferation is subject to complex controls, one of which is the differential expression of genes during the cell cycle. In the budding yeast, Saccharomyces cerevisiae, the periodic transcription of a number of genes which encode enzymes required for DNA synthesis is a prerequisite for cells to progress through S-phase; the restriction of histone gene transcription to late G1-early S-phase may also have evolved to regulate the yeast cell cycle. The regulatory circuit which controls the differential transcription of the yeast histone genes will be examined. Regulatory mutations affecting cell cycle-dependent transcription will be identified by screening for phenotypes associated with the altered expression of histone-lacZ fusion genes. Cis-acting mutations will be used to assess the roles of positive and negative histone promoter elements in periodic transcription. Trans-acting mutations which result in constitutive transcription during the cell cycle will identify regulatory genes which are required to maintain periodic transcription. The regulatory genes will be cloned by complementation of yeast mutants and the cloned genes will be used to study the functions of the proteins which they encode.